Toxic shock syndrome (TSS) is an acute febrile, exanthematous illness associated with multisystem failure including shock, renal failure, myocardial failure and adult respiratory distress syndrome (ARDS) (Todd et al., Drugs (United States) 39(6):856 (1990)). Symptoms of TSS include fever, pharyngitis, diarrhea, vomiting, mylagia, and a scarlet fever-like rash. TSS may progress rapidly (within hours) to signs of hypovolaemic hypotension such as orthostatic dizziness or fainting.
Patients with toxic shock syndrome usually have a staphylococcal infection such as a surgical wound infection or soft tissue abscess, or they may have TSS during menstruation associated with staphylococcal infection arising out of the use of a vaginal device such as tampons (Todd et al., supra).
Staphylococcus aureus and group A Streptococcus pyogenes are both known to produce toxic shock syndrome characterized by hypotension and multisystem organ failure (Barry et al., JAMA (United States) Jan. 24, 1992, 267(24):3315). Stappylococcus aureus is isolated in virtually all cases of both menstrual and non-menstrual TSS (Wright et at., Ann. Emerg. Med. (United States) 17(3):268 (1988)). In their original description of TSS, Todd et al., (Lancet 2:1116 (1978)) thought that the multisystem dysfunction in TSS was related to one or more new exotoxins. Schlievert et al. (J. Infec. Dis. 143:509 (1981)) and Bergdoll et al. (Lancet 1:1017 (1981)) independently discovered a toxin that they named pyrogenic exotoxin C and staphylococcal enterotoxin F, respectively. Further studies of these proteins found them to be identical, and in 1984 the term toxic shock syndrome toxin 1 (TSST-1) was adopted to describe the toxin (Wright et al., supra).
TSST-1 is a protein that has been found in 90% to 100% of women with menstrual TSS. TSST-1 also has been found to produce emesis and diarrhea in monkeys, fever in rabbits, and is an inducer of interleukin-1 synthesis. interleukin-1, an endogenous human pyrogen, produces fever and proliferation of lymphocytes (Ikejima et al., J. Clin. Invest. 73:1312 (1984)).
A patient with TSS will have a one- to four-day prosyndrome consisting of fever, nonrigorous chills, and mylagias, primarily involving the proximal limb, abdominal, lumbar, and cervical muscles. These muscles are frequently tender to the touch. Most patients also develop malaise, arthralagias, diarrhea or loose stools, emesis, headache, sore throat, and orthostatic dizziness. Another very common symptom of TSS is a brawny non-pitting edema of the face, eyelids, and extremities.
The dermatologic manifestations of TSS are well described (see e.g., Wright et al., supra) and are present in all cases. The classical rash is described as sunburn-like, blanching, nonpruritic, macular erythromderma. While the rash is usually diffuse, it may be localized to the trunk, extremities, or even to a small area in the inguinal or periheal region. The rash is usually present with the initial presentation of the patient and usually fades in about three days.
Other cutaneous manifestations are occasionally noted and include a papulopustular rash, petechiae, bullae, and areas of cutaneous hyperaesthesia. Surviving patients develop desquamation, mostly involving the hands and feet, about five to twelve days after the initial rash has resolved. Patients may also have delayed transient patchy alopecia or fingernail loss. Mucous membranes and the conjunctiva are frequently noted to be hyperemic, and a "strawberry" tongue has been frequently described.
Hypotension or orthostatic changes in blood pressure are seen in all patients with TSS by definition. The hypotension is multifactorial and likely is due to a combination of gastrointestinal losses, third space effect, and vasodilatation. Sinus tachycardia is usually present, although other ECG changes, including premature ventricular contractions on exertion, aberrant beats of bundle origin, first-degree heart block, flattened T waves, and non-specific ST-T wave changes, have been described as well.
Evidence of renal dysfunction is a common finding in TSS, frequently manifested by an increase in blood urea nitrogen (BUN) and creatinine, and decreased urine output. Dialysis has been required for acute tubular necrosis, a pathologic finding often present at necropsy. Sterile pyuria also has been noted in the majority of cases.
Neurologic manifestations, the most common being headache, are present in almost all cases. Examination of the cerebrospinal fluid will usually reveal normal glucose and protein levels but an occasionally elevated white blood cell count. Nonfocal neurologic abnormalities such as disorientation, confusion, hallucinations, and agitation occur in most patients and generally resolve within several days. Fatal cases have been reported to show cerebral edema and nonspecific neuronal changes.
Nonspecific laboratory abnormalities are seen frequently. The hematocrit in most patients with TSS is normal or mildly decreased, usually with a normochromic, normocytic red cell pattern. The white blood count will usually be increased with a large percentage of immature neutrophils. An absolute lympocytopenia is often present and normalizes over the course of the illness. Mild thrombocytopenia is common, although usually not severe. Common findings on clinical chemistry studies include hypoalbuminemia, hypocalcemia, hypophosphatemia, and hypomagnesiumemia. Hypotensive patients frequently are noted to have a metabolic acidosis with an increased lactate level.
Despite increasing knowledge about toxic shock syndrome, this illness continues to be a serious threat. Thus, there is a critical need for a novel means for the treatment of toxic shock syndrome.